Project Summary/Abstract Sudden-onset injuries?such as acquired injuries or insults to the brain, spinal cord, and major extremities?begin in an instant and typically cannot be reversed. While there is potential for varying degrees of physical, functional, psychosocial, and/or cognitive recovery with rehabilitation, these injuries often result in life-long and life-altering disabilities. Furthermore, many such injuries occur in individuals who are young, active, and otherwise healthy. With the approximately 2.58 million new injuries to the brain, spine, or limb that occur each year, and an estimated 14.45 million individuals living in the U.S. with long-term disabilities related to these conditions, sudden-onset injuries are some of the most common causes of morbidity in the U.S. Given the invaluable opportunity to improve outcomes for such a large number of individuals, there is a vital need to better understand the complex patterns of symptoms experienced by these individuals in the long term to inform high-quality clinical care. Symptom clustering science offers an ideal method to achieve this goal. This project?s broad, long-term objective is to understand the complex patterns of symptoms displayed after acquired injuries to the brain, spine, or limb, so that clinical care can be improved. Symptom clustering has proven useful as a strategy for personalized medicine with complex medical conditions, such as cancer. However, there are several significant gaps in the literature, including the need to expand these methods to other clinical groups, define the characteristics of symptom clusters, identify instruments and metrics for measuring symptom clusters, and apply novel analytic strategies for detecting symptom clusters. This work will leverage over a decade of the investigators? prior qualitative and quantitative work on several large, multi-site studies with these clinical populations. In particular, existing data sets will be reanalyzed using new symptom clustering techniques. Results from these new analyses will be used to identify and characterize the most important symptom clusters for individuals with acquired disabilities. Then, a new, more diverse sample of individuals with acquired injuries to the brain, spine, or limb will be collected and evaluated to examine the generalizability and stability of these symptom clusters for use within and across rehabilitation populations. Last, the findings will be used to generate guidelines and clinical tools to translate symptom clusters into clinical practice. This work will be accomplished through four aims. Aim 1: Identify transdiagnostic and condition-specific symptom clusters present in individuals with traumatic injuries. Aim 2: Explore the generalizability and reproducibility of the symptom clusters identified in Aim 1 in a diverse sample of individuals with acquired disabilities. Aim 3: Examine longitudinally the stability and predictive utility of symptom clusters in a diverse sample of individuals with acquired disabilities. Aim 4: Develop guidelines and clinical tools for assessing and interpreting symptom clusters in individuals with acquired disabilities.